术中亚低温携氧灌注诱导的CIRP对肝脏的保护作用及机制研究

项目名称： 术中亚低温携氧灌注诱导的CIRP对肝脏的保护作用及机制研究

项目编号： No.U1403222

项目类型： 联合基金项目

立项/批准年度： 2015

项目学科： 管理科学

项目作者： 叶啟发

作者单位： 武汉大学

项目金额： 215万元

中文摘要： 在自体肝移植和异体肝移植中，如何有效维护肝脏质量和修复肝脏损伤是核心问题。自体血携氧灌注评价和维护离体器官正成为全新的方向。亚低温可减轻氧化应激，增强组织对缺血及再灌注的耐受力。推测自体血携氧灌注结合亚低温可减轻术中肝脏缺血再灌注损伤，但具体机制有待进一步研究。本课题组前期已建立猪肝脏在体和离体自体血携氧灌注的模型，并证明32℃亚低温保存的肝脏中有冷诱导RNA结合蛋白（CIRP）的表达。CIRP参与了TRX基因的转录后调控的过程，TRX进一步淬灭ROS活性减轻氧化应激。亚低温诱导的CIRP可能通过稳定TRX mRNA的翻译，减轻缺血缺氧及氧化应激对组织的损伤。我们拟使用过表达质粒、siRNA正反双向调节CIRP的表达，研究CIRP在亚低温灌注系统中对热缺血肝脏、脂肪肝的保护作用及机制。探讨亚低温携氧灌注对术中存在基础病变肝脏的修复作用，为存在基础病变肝脏的术中在体及离体保存提供新方法。

中文关键词： 肝移植；携氧灌注；亚低温；冷诱导RNA结合蛋白

英文摘要： To those have pathological lesions or warm ischemia injury graft, how to effectively maintain its quality and repair its damage is the key problem need to be solved in autologous or allgeneic liver transplantation. The uses of autologous blood oxygenate perfusion to evaluate and maintain in vitro graft function is becoming a new direction. Sub-thermia can reduce oxidative stress damage on liver, kidney and brain, enhance their tolerance to ischemia and reperfusion. Our team has successfully established a stable model pig liver in vitro and in vivo autologous blood oxygenate perfusion system. It's supposed that combined autologous blood oxygenates perfusion to sub-thermia can reduce hepatic ischemia-reperfusion injury, but the exact mechanism remains to be further studied. Previous studies have shown that there have cold-induced RNA binding protein(CIRP) expressed in hypothermia(32℃) preserved liver. TRX gene can quench ROS activity to reduce oxidative stress, and CIPR have involved in TRX gene transcriptional regulation process. Thus, we deduce CIRP may reduce ischemic and oxidative stress injury through stabilize TRX mRNA translation. We intend to use the over- expression plasmid and siRNA to positive and negative regulate the expression of CIRP, to research CIRP protective effect and mechanism in fatty liver and warm ischemia liver in sub-thermia perfusion system. To investigate the repair function in pathological lesion liver of sub-thermia perfusion system, and provide a new preserving methods for the injuried liver.

英文关键词： NULL